A randomized clinical trial comparing tacrolimus and sirolimus maintenance monotherapy following kidney transplantation ME Cho1, X Zhao2, MS Ring1, RB Mannon3, AD Kirk4 1 Kidney Disease Branch, NIDDK; 2Office of the Director, NIDDK, NIH, Bethesda, MD; 3University of Alabama, Birmingham, AL; 4Emory University, Atlanta, GA Background: Both sirolimus (Rapa) and tacrolimus (FK) are effective in preventing renal allograft rejection when used as part of a multidrug regimen, but there have been no studies directly comparing these agents as monotherapies. Methods: In order to investigate whether there was a clear advantage to either drug, we enrolled 31 patients in a phase II trial using Thymoglobulin and methylprednisolone induction followed by combination therapy with both Rapa and FK for 6 months. At 6 months, those without rejection on protocol biopsy with good tolerance to both drugs were randomized either Rapa or FK monotherapy. Primary outcome was renal graft function over time, using linear mixed model to calculate the least mean square values of serum creatinine for repeated measurements. The secondary outcomes included safety and tolerability profiles and renal graft biopsy results. Results: Out of 31 patients, 7 were randomized to Rapa and 8 to FK. The remaining 16 patients could not be randomized due to Rapa intolerance oral ulcers (1); hyperlipidemia (2); arthropathy (3), rejection on protocol biopsy (4), or unrelated issues (6). The mean follow-up was 4 yrs post randomization. Their mean nadir serum Cr (mg/dL) was 1.03 in Rapa group and 1.17 in FK group and remained stable over 54 months without significant increase. There were no differences in the rates of biopsy diagnoses of IF/TA, rejection, or BK nephropathy in the two groups, based on a mean of 3.5 biopsies per patient over a mean of 1.4-year period. Serum triglycerides levels were significantly higher in the Rapa group between months 6-24, and the absolute lymphocyte count remained significantly lower in Rapa group between months 12-30. The incidence of post transplant diabetes was similar in both groups. Conclusion: In patients selected for their stability and tolerance to either drug, both Rapa and FK monotherapy provided similar prophylaxis from rejection without differing long-term consequences over a 4 year follow-up period. FK was associated with fewer dose limiting consequences.